HIV research hit as SA-tested experimental vaccine fails to protect users
The decades-long research for an HIV vaccine has hit another setback after another vaccine candidate failed in a large-scale African study.
On Tuesday, Johnson & Johnson (J&J) announced that its four-year investigation, known as the “Imbokodo trial”, which involved 2,600 women in SA and its four neighbouring countries — Zimbabwe, Mozambique, Malawi and Zambia — offered no convincing protection against HIV infection in the trial. The study will, as a result of this, be discontinued.
Researchers say the 25% efficacy shown by the experimental vaccine was too low to make it useful. No safety concerns were reported.
In these countries, women and girls account for about 60% of all new infections.
“Though this is certainly not the study outcome for which we had hoped, we must apply the knowledge learnt from the Imbokodo trial,” said Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases (NIAID), which funded the study along with the Melinda Gates Foundation.
The Imbokodo trial, which uses the same adenovirus platform used in J&J's Covid-19 shot, started in 2017 in about 26 sites across the five African countries. It is based on “mosaic” immunogens—vaccine components designed to induce immune responses against a wide variety of global HIV strains. The vaccine candidate used a strain of common-cold virus (adenovirus serotype 26, or Ad26), engineered to not cause illness, but to deliver antigens to spur an immune response.
Earlier research indicated the vaccine was both well-tolerated and could induce an anti-HIV immune response. Imbokodo participants received four vaccinations during a one-year period. This included four doses of the investigational quadrivalent vaccine. J&J said it would, however, continue with a companion study, the Phase 3 Mosaico trial, which is testing the safety and efficacy of a different investigational HIV vaccine among men who have sex with men and transgender populations in the US and Europe. The Mosaico study is expected to be completed in March 2024.
While Imbokodo study participants are still being informed of the findings, researchers say the analysis of the study will continue and they are convinced that the investigation has provided sufficient data for further immunological research.
HIV advocacy group Avac called for a comprehensive global strategy to develop HIV vaccines.
“This is in no way the end of the search for an HIV vaccine,” said Mitchell Warren, executive director of Avac. “We still hope for a positive outcome from the ongoing Mosaico and PrEPVacc studies.”
PrEPVacc is an African-led HIV prevention study, which combines the evaluation of experimental HIV vaccines and PrEP at the same time.
“Yet, now more than ever, the vaccine field needs diversity, creativity, and even more collaboration, in deciding what comes next as research priorities as there are no other vaccine candidates now on a clear track to licensure. The field must focus on new hypotheses driven by this result and the recent antibody-mediated prevention study results, both of which showed some trends towards efficacy.
“For the last two decades, we have seen HIV prevention trials reporting annual incidence rates of 4% or higher among women trial participants in various east and southern African countries. Sadly, J&J noted a high rate of HIV infections in this trial as well. There is a moral and ethical obligation to provide women living in contexts of HIV risk with prevention options that work for them.
“The Imbokodo study is yet another stark reminder of the need to work harder and faster to roll out effective HIV prevention options at scale to the people who need them most,” said Warren.
Public health experts have also called for renewed commitment within the HIV vaccine field to build on lessons learnt from Covid-19 vaccine development.
Stacey Hannah, Avac’s director of research engagement, said: “Just as decades of HIV research paved the way for effective Covid-19 vaccines, HIV vaccine developers now need to draw on the creativity, speed, agility and decision-making of Covid-19 vaccine development in product development, trial design and regulatory pathways. Avac calls on donors, research groups and industry to join in strategic discussions with civil society and trial communities to map out a comprehensive strategy for the future of HIV vaccine research and trial designs.”
A renewed commitment to this type of engagement within the HIV vaccine field would build on lessons learnt from Covid-19 vaccine development and lead to a strategy that is co-ordinated, appropriately resourced, includes relevant target product profiles, and commits to share data across research groups and trials.